The studies on temperature responsive polymers showing a reversible change of from hydrophilicity on a low temperature side to hydrophobicity on a high temperature side on temperature stimulation are receiving attention. The polymers are expected to be applied to a drug carrier, a wound dressing material, an artificial muscle, a microcapsule, a biomachine, a biosensor, a separation membrane, and the like, by utilizing the property thereof, i.e., inclusion of a large amount of water.
As the temperature responsive polymer, a polymer of 2-methoxyethyl vinyl ether (MOVE) has been known. A vinyl ether copolymer containing an oxyethylene unit, such as MOVE, is excellent in biocompatibility and is expected to be applied to a medical material (PTL 1). However, a homopolymer of MOVE has a temperature, at which the phase transition occurs, i.e., a lower critical solution temperature (LCST) of approximately 65° C., and thus it is difficult to apply the homopolymer to a medical material that utilizes temperature responsiveness around body temperature.
As another polyvinyl ether containing an oxyethylene unit, a polymer of 2-hydroxyethyl vinyl ether (HEVE) has been known. The polymer of HEVE has higher hydrophilicity due to the presence of a hydroxyl group on the side chain thereof and the small number of carbon atoms of the side chain, and is expected to have utility as a medical material excellent in biocompatibility. Furthermore, diethylene glycol monovinyl ether (DEGV) with an extended oxyethylene unit while retaining the hydrophilicity also has hydrophilicity that is equivalent to or higher than that of HEVE, and is expected to be excellent in biocompatibility. However, these homopolymers are water soluble and do not show temperature responsiveness, and thus it is difficult to apply the homopolymers to a medical material that utilizes temperature responsiveness around body temperature.
It has been known that a copolymer exhibiting temperature responsiveness can be obtained through random copolymerization of HEVE with 2-hydroxybutyl vinyl ether (HBVE) having a larger number of carbon atoms than HEVE (PTL 2). However, a homopolymer of HBVE has a LCST of approximately 44° C., and the LCST is further increased by the copolymerization with HEVE having higher hydrophilicity. Therefore, it is difficult to apply the polymer to a medical material that utilizes temperature responsiveness around body temperature.
It is also known that a temperature responsive polymer is obtained through random copolymerization of HEVE with a hydrophobic vinyl ether that does not exhibit temperature responsiveness. For example, it has been known that a random copolymer of HEVE and hydrophobic isobutyl vinyl ether (IBVE) and a random copolymer of HEVE and 6-hydroxyhexyl vinyl ether exhibit sharp temperature responsiveness (NPL 1). However, an isobutyl group containing no polar group and a 6-hydroxyhexyl group having a large number of carbon atoms have high hydrophobicity, and it is expected that copolymers obtained by using these comonomers are inferior in biocompatibility.
Furthermore, the copolymers are synthesized through living cationic polymerization using a monomer having a hydroxyl group protected by a silyl group, and the synthesis method requires a protection step for the hydroxyl group and a deprotection step after the polymerization, and thus includes a large number of process steps. Moreover, since the living cationic polymerization is generally performed at a low temperature of 0° C. or less, the temperature control cannot be easily performed in an industrial scale due to the reaction heat, and if is difficult to produce the copolymers industrially efficiently at low cost.
A hydroxyl group-containing vinyl ether, such as HEVE, DEGV, and HBVE, is radically polymerizable, and a copolymer with an alkyl vinyl ether, such as IBVE, can be produced (PTL 2). However, since the hydroxyl group-containing vinyl ether and the alkyl vinyl ether, such as IBVE, have large differences in radical polymerizability and in hydrophilicity and hydrophobicity between them, the polymerization control (e.g., control of the polymer formation and the compositional ratio) is difficult and which makes it difficult to achieve a uniform distribution of the hydrophilic portion and the hydrophobic portion, and thus the copolymer obtained through radical polymerization cannot exhibit sharp temperature responsiveness.
Accordingly, such a comonomer is demanded that can lower the LCST without impairing the biocompatibility of the hydroxyl, group-containing vinyl ether and can be easily polymerized, but a suitable comonomer has not yet been found for copolymers of vinyl ethers.
Although a hydroxyl group-containing vinyl ether is radically polymerizable, the reactivity thereof is largely different from that of a general radically polymerizable vinyl monomer, such as a styrene derivative and a (meth)acrylic acid derivative, resulting in difficulty in polymerization control in copolymerization with a hydrophobic radically polymerizable vinyl monomer other than a vinyl ether, and the temperature responsiveness of the copolymer has not been investigated.